JP7433908B2 - Yarrow Fresh Plant Squeezed Juice Concentrate, Manufacture, and Use - Google Patents

Description

The present invention relates to a Yarrow fresh plant juice concentrate treatment that can be stored for long periods of time without the need for heat treatment, preservatives or other additives. Furthermore, the present invention relates to a gentle method of producing such a Yarrow fresh plant press concentrate. Yarrow fresh plant juice concentrate is used in cosmetic compositions, pharmaceutical compositions, food compositions or food supplements.
The invention also relates to new aspects of the use of Yarrow. The present invention provides the use of Yarrow to stimulate the expression of heat shock proteins and/or antimicrobial peptides in skin cells. Furthermore, the use of yarrow to increase the heat tolerance of the skin is described.

Achillea millefolium is a traditional medicinal plant. Typical ingredients include, for example, essential oils, sesquiterpenes, phenolic compounds such as flavonoids, phenolic carboxylic acids, and betaines. Examples of phenolic carboxylic acids include chlorogenic acid and various dicaffeoylquinic acids.
Yarrow is used in the form of an extract. For the production of liquid extracts, for example, fresh (not dried) plants are used, ie the starting plant material generally has to be cultivated or harvested close to the production area. Mature plants must be harvested and pressed and bottled in a timely manner (usually within one day) to prevent spoilage and microbial contamination.
Yarrow juice obtained in this way can be used for mild spasmodic discomfort in the gastrointestinal tract, including, for example, bloating and loss of appetite. Yarrow is also used in skin creams due to its favorable properties in wound healing.

Yarrow extract is already widely used in cosmetics for topical application. These are extracts made from dry drugs. Drying provides time independence from seasonal harvest periods and protection from possible spoilage. Dried plant material can be stored and transported more easily and cost-effectively. However, during the drying of the plant material and during the production of the extract (extraction, if necessary heat supply and distillation of the extractant under heat, usually followed by concentration), the A local change occurs in the spectrum of the constituents.
The industrial production of fresh yarrow plant juice involves harvesting the plant or plant parts to be pressed, cleaning and chopping, steam treatment for inactivation of plant enzymes and decomposition of the plant material, pressing under pressure, This is commonly done by filtration or centrifugation, short-term heating at very high temperatures for sterilization, and aseptic filling (Deutsche Apothekerzeitung 2011, p. 93 ff.). Such fresh plant juices usually contain 2-6% by weight of dry extract or juice. This is a mild process in which high temperatures are used for only short periods of time. Furthermore, relatively few work steps are required. This is to ensure the protection of sensitive and biologically active ingredients such as antioxidants.

The disadvantage is that the fresh plant juice obtained can only be stored in closed containers, otherwise there is a risk of microbial contamination. As a result, fresh plant juice is difficult to handle, especially for the end consumer. This is due to the fact that it is necessary to use it up completely or to add undesirable preservatives to the fresh plant juice in order to protect it from spoilage.

Therefore, one object of the present invention is to provide a yarrow extract capable of long-term storage and a method for producing such an extract. A further object is to provide a yarrow extract that can be stored without the use of preservatives or other additives. The ingredient profile should not be affected by the manufacturing process or storage. Furthermore, an aqueous yarrow extract should be provided which offers advantageous additional applications compared to the application possibilities known in the state of the art. The state of the art describes active substances that stimulate heat shock proteins and/or skin AMPs. Nevertheless, there is a need for new naturally derived, well-tolerated HSP and/or AMP stimulants that are easy to incorporate into cosmetic formulations.
Therefore, the present invention provides for 100% by weight of Yarrow fresh plant pressed juice concentrate:
10 to 100% by mass of yarrow fresh plant pressed juice dry residue,
A fresh plant juice concentrate of Yarrow comprising or consisting of 0 to 90% by weight of water and 0 to 90% by weight of a carrier.

Furthermore, the present invention
preparing a Yarrow fresh plant press; and concentrating the Yarrow fresh plant press;
A method for producing a Yarrow fresh plant juice concentrate, preferably a concentrate of the invention as described herein, comprising or consisting of the steps of.
The present invention provides the use of Yarrow to stimulate the expression of heat shock proteins and/or antimicrobial peptides in skin cells.
The invention further provides the use of yarrow for increasing the heat tolerance of the skin.
Furthermore, the invention relates to the use of the fresh plant juice concentrate of the invention as a medicine.

Surprisingly, the concentrate of Yarrow fresh plant press juice dry residue has a long shelf life. This is the case even if preservatives or various processing procedures at elevated temperatures for preservation, such as pasteurization, are excluded. The method of the present invention allows for a method that maintains a mild (ie, no prolonged exposure to higher temperatures) component profile. In particular, reverse osmosis, freeze drying, spray drying or a combination of these concentration processes can be used.
The use of one or more of these methods can prevent undesirable practices for concentrating fresh plant juices, such as removing water by distillation. Removal of water by distillation requires longer process times at elevated temperatures (70-80° C.) and usually leads to changes in the component profile. Heat-sensitive components may be altered or degraded thereby.

It has also been found that Yarrow in general, and in particular the concentrates and Yarrow fresh plant juice of the present invention, are suitable for cosmetic compositions. Yarrow, especially Yarrow fresh plant juice, upregulates several heat shock proteins (HSPs) at the genetic level. For example, HSP70 is not upregulated, but HSP27 is upregulated at the gene level. Furthermore, it was surprisingly found that Yarrow, especially Yarrow fresh plant juice, upregulates antimicrobial proteins and peptides (AMPs), such as β-defensin 1 and S100 calcium-binding protein A8, at the genetic level. It was done. Hsp27 is known to confer heat tolerance and cytoprotection and aid cell survival under stress conditions. On the other hand, AMPs can be used as topically applied biocides, especially for the treatment of multidrug-resistant pathogens and the treatment of skin and wound infections. Furthermore, its use in tumor therapy is also envisaged. This leads to advantageous applications of yarrow, especially in the framework of cosmetic and pharmaceutical compositions, which are preferably applied topically.

The term "yarrow" as used herein also refers to the Achillea millefollium herb or members of the Achillea millefollium group by Yarrow Herb and Hager's Handbuch der pharmazeutischen Praxis, Springer Verlag. Yarrow may be present as an untreated plant or in various preparations, such as Yarrow fresh plant juice or Yarrow fresh plant juice concentrate.

"Yarrow fresh plant pressed juice" and "Yarrow fresh plant pressed juice concentrate" have a relatively high content of polyphenols, especially the monocaffeoylquinic acid group (chlorogenic acid [3-O-caffeoylquinic acid, CAS 327-97-9], neochlorogenic acid [5-O-caffeoylquinic acid, CAS 906-33-2] and cryptochlorogenic acid [4-O-caffeoylquinic acid, CAS 905-99-7]. ), and the dicaffeoylquinic acid group (1,5-di-O-caffeoylquinic acid, [cynarin, CAS 30964-13-7], 3,4-di-O-caffeoylquinic acid [isochlorogen acid B, CAS 14534-61-3], 3,5-di-O-caffeoylquinic acid [isochlorogenic acid A, CAS 2450-53-5] and 4,5-di-O-dicaffeoylquinic acid characterized by the presence of phenolic carboxylic acids, including [isochlorogenic acid C, CAS 57378-72-0]). Polyphenols are known for their excellent antioxidant effects.

Yarrow fresh plant juice is available for example from Schoenenberger (Information for users: Natural unadulterated medicinal plant juice yarrow for use by adults and adolescents over 12 years of age, Walther Schoenenberger Pflanzensaftwerk GmbH & Co. KG, Magstadt (Germany) ), July 2014). Yarrow fresh plant juice is produced from fresh Yarrow herb harvested during the flowering period. It is marketed for oral use as a traditional herbal product for mild spasmodic discomfort in the gastrointestinal tract, including bloating and loss of appetite. Yarrow fresh plant juice is a brown, clear to slightly opalescent liquid that typically contains 94.5-96.5% water and 3.5-5.5% dry residue by weight. contains.
Yarrow fresh plant juice concentrate may be produced, for example, from Yarrow fresh plant juice by a concentration process. For example, Yarrow fresh plant juice concentrate is produced from Schoenenberger Yarrow fresh plant juice by concentration. However, it is clear that any Yarrow extract can be used, especially Yarrow fresh plant juice.

The term "dry residue" or "dry substance" refers to the substances remaining after drying, such as water and/or solvents of Yarrow fresh plant press juice or Yarrow fresh plant press concentrate, according to the definition of analytical chemistry. Used for free fractions. The drying process is essentially complete, i.e. the residual water and/or solvent content of the substance to be analyzed, such as Yarrow fresh plant juice or Yarrow fresh plant juice concentrate, is preferably ≦1 mass %, preferably ≦0.5% by weight, ≦0.1% by weight, more preferably ≦0.01% by weight. Drying is preferably carried out in a mild process, for example at a temperature slightly above the boiling point of the water, solvent or solvent mixture, if applicable, such as ≦10°C, ≦5°C or ≦2°C. Alternative drying methods include freeze drying, drying under partial vacuum, use of a desiccant, or a combination of the above methods.

The term "extract" as used herein relates to thickened or dried extracts of plant material, particularly yarrow. Therefore, the extract is a liquid. Yarrow fresh plant juice represents such an extract. Yarrow fresh plant juice preferably contains ≦8% by weight dry residue, preferably ≦7.5% by weight dry residue, ≦7% by weight dry residue, ≦6.5% by weight dry residue, ≦ Contains 6% by weight dry residue, or ≦5.5% by weight dry residue. More preferably, the Yarrow fresh plant juice comprises from 3.5% to 5.5% by weight dry residue.

The term "concentrate" as used herein relates to solids or liquids containing relatively low proportions of additional fillers and/or solvents. Thus, Yarrow fresh plant juice concentrate is characterized by a higher content of dry residue than Yarrow fresh plant juice. Yarrow fresh plant juice concentrate contains ≧10% by weight dry residue, preferably ≧15% by weight dry residue, ≧20% by weight dry residue, ≧25% by weight dry residue, ≧30% by weight dry residue, ≧40% by weight dry residue, ≧50% by weight dry residue, ≧60% by weight dry residue, ≧70% by weight dry residue, ≧80% by weight dry residue, or ≧90% by weight dry residue. has. Concentrates are produced in a gentle manner, i.e. in comparison with extracts, the content spectrum of essentially the same constituents remains suitably concentrated (according to the ratio of dry residue concentrate divided by dry residue extraction). do. Essentially, the same content spectrum of the constituents is determined by the individual content of the constituents of ±10% by weight in the concentrate, preferably ±5% by weight in the concentrate, more preferably ±2% by weight in the concentrate. related to deviation. For example, if the Yarrow fresh plant juice has a dry residue of 8% by weight and the Yarrow fresh plant juice concentrate has a dry residue of ≧10% by weight, then the individual components in the concentrate or the concentration of the component is increased by at least a factor of 10 divided by 8.

The solid Yarrow fresh plant pressed juice concentrate contains 100% by mass of Yarrow fresh plant pressed juice concentrate, 10 to 100% by mass of Yarrow fresh plant pressed juice dry residue, 0 to 90% by mass of water, and 0 to 90% by weight of carrier based on 100% by weight of Yarrow fresh plant pressed juice concentrate. Preferably, the solid Yarrow fresh plant juice concentrate is produced directly, ie without pre-concentration, with the optional addition of the carriers mentioned herein. Such a solid Yarrow fresh plant juice concentrate comprises 10-100% by weight of Yarrow fresh plant juice dry residue, 0-10% by weight water, and 0-90% by weight of carrier. More preferably, the solid Yarrow fresh plant press concentrate comprises 10-50% by weight of Yarrow fresh plant press dry residue, 0-10% by weight water, and 50-90% by weight of carrier.

The liquid Yarrow fresh plant press juice concentrate is preferably produced by reverse osmosis and subsequent addition of a liquid carrier, preferably from 10 to 70% by weight of Yarrow fresh plant press dry residue, from 0 to 90% by weight. of water, 0-90% by weight of liquid carrier, and 0-5% by weight of preservatives and/or stabilizers. Optional liquid carriers are as described below and include, for example, glycerol, propylene glycol, butylene glycol, 1,3-propanediol, 1,2-pentanediol, 1,2-hexanediol, And after concentration, optional preservatives and/or stabilizers are also added.
Preference is given to 10 to 50% by weight of Yarrow fresh plant juice dry residue, 0 to 90% by weight of water, 0 to 50% by weight of carrier, and 0 to 3% by weight of preservatives and/or stabilizers. is a liquid yarrow fresh plant pressed juice concentrate containing. The advantages of solid or liquid Yarrow fresh plant juice concentrate are simple and cost-effective production, good shelf life, easy handling and administration, and, if desired, standardization.
The dosage of yarrow fresh plant juice concentrate (solid or liquid) in cosmetic compositions, especially cosmetic compositions for cleansing and care of the skin and hair, is from 0.0001 to 10% by weight, preferably 0. 0.001 to 5% by weight, particularly preferably 0.005 to 3% by weight.

The cosmetic composition preferably comprises from 0.0001 to 10% by weight, preferably from 0.001 to 5% by weight, particularly preferably from 0.005 to 3% by weight of Yarrow fresh plant juice concentrate, wherein The concentrate may be obtained by freeze drying, spray drying or reverse osmosis. These cosmetic compositions may also contain combinations of ingredients as described in Example 5, Table 12, Compositions 1 to 11, with the freedom to choose the individual amounts of each ingredient other than Yarrow fresh plant juice concentrate. Contains one of the following. It is clear that the combination of perfumes used is not limited to the perfume oils PFO1 and PFO2, but other perfumes or combinations of perfumes known to the person skilled in the art can be used.

Alternatively, a gel toothpaste can be presented. The gel toothpaste also contains from 0.0001 to 10% by weight, preferably from 0.001 to 5% by weight, particularly preferably from 0.005 to 3% by weight of Yarrow fresh plant juice concentrate, where the concentrate may be obtained by freeze drying, spray drying or reverse osmosis. This composition also combines the ingredients described in Example 5, Table 13, Compositions I, II and III, with the freedom to choose the individual amounts of each ingredient other than Yarrow fresh plant juice concentrate. Contains one of the following.

Alternatively, ready-to-use fluoride mouthwashes can be presented. The ready-to-use fluoride mouthwash also comprises from 0.0001 to 10% by weight, preferably from 0.001 to 5% by weight, particularly preferably from 0.005 to 3% by weight of Yarrow fresh plant juice concentrate. , where the concentrate may be obtained by freeze drying, spray drying or reverse osmosis. This composition also combines the ingredients described in Example 5, Table 14, Compositions I, II and III, with the freedom to choose the individual amounts of each ingredient other than Yarrow fresh plant juice concentrate. Contains one of the following.

Alternatively, the Yarrow fresh plant juice concentrate of the present invention consists of the mentioned ingredients. In this case no other ingredients are present. Therefore, the Yarrow fresh plant pressed juice concentrate of the present invention contains 100% by weight of Yarrow fresh plant pressed juice concentrate, 10 to 100% by weight of Yarrow fresh plant pressed juice dry residue, and 0 to 90% by weight. % water, and 0 to 90% by weight carrier. Preferably, the Yarrow fresh plant juice concentrate of the present invention comprises 10 to 50% by weight of Yarrow fresh plant juice dry residue, 0 to 50% by weight of water, and 0 to 50% by weight of carrier; 20% by weight of Yarrow fresh plant pressed juice dried residue, 0-80% by weight of water and 0-80% by weight of carrier; 10-15% by weight of Yarrow fresh plant pressed juice dried residue, 0-85% by weight of water and 0 to 85% by weight of carrier. More preferably, the Yarrow fresh plant press concentrate of the present invention consists of 10-15% by weight of Yarrow fresh plant press dry residue and 85-95% by weight of water and/or carrier.
According to one embodiment, the carrier is a solid carrier, in particular maltodextrin, dextrin or cyclodextrin, and/or a liquid carrier, in particular glycerol, propylene glycol, butylene glycol, 1,3-propanediol, 1,2- Pentanediol, 1,2-hexanediol or 1,2-octanediol.

The addition of carriers or carrier materials allows the product properties (eg flowability) and/or the standardization to be influenced to a certain extent. Additionally, the resulting matrix particles also provide some protection against unstable components. The carrier is preferably selected from those used in the concentration process. For example, if concentration is carried out by spray drying, solid carriers, especially the polysaccharides listed below, may be used as suitable materials. This polysaccharide then serves as a carrier in the cosmetic composition, eg, a carrier that imparts desired properties to the composition. More preferably, the carrier substance is used in the desired dosage form, for example in the context of a concentrate for use in cosmetic compositions, pharmaceutical compositions, food compositions or food supplements.
It is clear that one or several carriers may be included. These carriers may be solid or liquid (at 25° C. and 1013 mbar). Individual substances or mixtures of substances may be used as carriers.

Preferred solid carriers are degraded starches, chemically or physically modified starches, modified celluloses, gum arabic, gum ghatti, tragacanth, karaya, carrageenan, guar gum, locust bean gum, alginates, pectin, inulin or xanthan gum. Generally, polysaccharides such as maltodextrin, dextrin, oxidized starch or lactose, collagen, fumed silica (such as Aerosil®), cashew gum, gum arabic or the like may be used. Mixtures of the aforementioned solid carriers may also be used in the context of the present invention. Maltodextrin is a particularly preferred solid carrier.
The degree of starch degradation is usually indicated by the index "dextrose equivalent" (DE), which has a threshold of 0 for long-chain glucose polymers and 100 for pure glucose. Polysaccharides, especially maltodextrins with a DE value in the range 5-20, preferably in the range 15-20, are again particularly advantageous.
Examples of preferred liquid carriers are ethanol, diacetin, isopropyl alcohol, glycerol, 1,2-propylene glycol, 1,3-propanediol, 1,3-butylene glycol, triacetin and mixtures thereof.

Advantageous carriers in the preferred (preferably spray-dried) concentrates of the invention are in particular silicon dioxide (silicic acid, silica gel), carbohydrates and/or carbohydrate polymers (polysaccharides), cyclodextrins, starches, degraded starches (starch hydrolysates), chemically or physically modified starches, modified celluloses, gum arabic, gum ghatti, tragacanth, karaya, carrageenan, guar gum, locust bean gum, alginates, pectin, inulin or xanthan gum. Preferred starch hydrolysates are maltodextrins and dextrins. Particularly preferred carriers are silicon dioxide, gum arabic and maltodextrins, with maltodextrins having DE values in the range from 5 to 20 being preferred.

Preferred or particularly preferred carriers also have the advantage of being tasteless or essentially tasteless. As a result, these precursors can range from having no or not significantly affecting other organoleptic properties, in particular aroma and taste profiles (apart from unpleasant taste impressions to be masked), to The concentrates of the invention can be used in a number of different product types and preparations.
According to one embodiment, the Yarrow fresh plant juice concentrate further comprises preservatives and/or stabilizers.
Any number of preservatives and/or stabilizers may be used.
Preservatives used in the context of the present invention typically have some, preferably all, of the following properties: They are toxicologically harmless, well tolerated by the skin, stable, essentially completely odorless, and easily and inexpensively (i.e., readily available extractables). ) can be manufactured. Preservatives also have antimicrobial properties. Suitable preservatives are found, for example, in WO2006/045743.

Examples of suitable preservatives are benzoic acid, esters and salts of benzoic acid, sorbic acid and its salts, propionic acid and its salts, salicylic acid and its salts, dormaldehyde and paraformaldehyde, 2-hydroxybiphenyl ether and its salts, 2-Zinc sulfide pyridine N-oxide, inorganic sulfite and bisulfite, sodium iodate, chlorobutanol, 4-ethylmercury(II)-5-amino-1,3-bis(2-hydroxybenzoic acid), its esters and salt, dehydroxyacetic acid, formic acid, 1,6-bis(4-aminodino-2-bromophenoxy)-n-hexane and its salts, sodium salt of ethylmercury(II)-thiosalicylic acid, phenylmercury and its salts, 10 -Undecylenic acid and its salts, 5-amino-1,3-bis(2-ethylhexyl)-5-methylhexahydropyrimidine, 5-bromo-5-nitro-1,3-dioxane, 2-bromo-2-nitro -1,3-propanediol, 2,4-dichlorobenzyl alcohol, N-(4-chlorophenyl)-N'-(3,4-dichlorophenyl)urea, 4-chloro-m-cresol, 2,4,4' - Trichloro-2'-hydroxydiphenyl ether, 4-chloro-3,5-dimethylphenol, 1,1'-methylene-bis(3-(1-hydroxymethyl-2,4-dioxoimidazolidin-5-yl) urea), poly(hexamethylene biguanide) hydrochloride, 2-phenoxyethanol, hexamethylenetetramine, 1(3-chloroallyl)-3,5,7-triaza-1-azoniaadamantane chloride, 1(4-chlorophenoxy)1 (1H-imidazol-1-yl)-3,3-dimethyl-2-butanone, 1,3-bis(hydroxymethyl)-5,5-dimethyl-2,4-imidazolidinedione, benzyl alcohol, octopirox , 1,2-dibromo-2,4-dicyanobutane, 2,2'-methylene-bis(6-bromo-4-chlorophenol), bromochlorophene, 5-chloro-2-methyl-3(2H) isothiazolinone and mixtures of 2-methyl-3(2H) isothiazolinone with magnesium chloride and magnesium nitrate, 2-benzyl-4-chlorophenol, 2-chloroacetamide, chlorhexidine, chlorhexidine acetate, chlorhexidine gluconate, chlorhexidine hydrochloride, 1-phenoxypropane -2-ol, N-alkyl (C12-C22) trimethylammonium bromide and chloride, 4,4-dimethyl-1,3-oxazolidine, N-hydroxymethyl-N-(1,3-di(hydroxymethyl)-2) , 5-dioxoimidazolidin-4-yl)-N'-hydroxymethylurea, 1,6-bis(4-amidinophenoxy)-n-hexane and its salts, glutaraldehyde, 5-ethyl-1-aza- 3,7-dioxabicyclo(3.3.0)octane, 3-(4-chlorophenoxy)-1,2-propanediol, high amine, alkyl-(C8-C18)-dimethylbenzylammonium chloride, alkyl-( C8-C18)-dimethylbenzylammonium bromide, alkyl-(C8-C18)-dimethylbenzylammonium saccharinate, benzyl hemiformal, o-cymen-5-ol, sodium hydroxymethylaminoacetate or sodium hydroxymethylaminoacetate, and mixtures of the aforementioned substances.

Other suitable preservatives include parabens. Parabens are esters of parahydroxybenzoic acid such as methylparaben, ethylparaben, n-propylparaben, n-butylparaben, isobutylparaben, and mixtures. Parabens, alone or in combination, may be used as preservatives, especially in cosmetic and pharmaceutical compositions. A preferred paraben combination for the aforementioned composition comprises 18% by weight methylparaben and 0.02% by weight propylparaben. Parabens have both antibacterial and fungicidal effects.

Furthermore, according to the invention, preservatives or preservative excipients commonly used in cosmetics are suitable, for example dibromodicyanobutane (2-bromo-2-bromomethylglutarodinitrile), 3-iodo-2 -Propynylbutyl carbamate, 2-bromo-2-nitropropane-1,3-diol, imidazolidinyl urea, 5-chloro-2-methyl-4-isothiazolin-3-one, 2-chloroacetamide, benzalkonium chloride, benzyl Alcohol and formaldehyde splitter.
Furthermore, phenylhydroxyalkyl ethers, especially the compound known as phenoxyethanol, are suitable as preservatives due to their bactericidal and fungicidal effects against some microorganisms.

Stabilizers are used in the context of the invention to protect the compositions of the invention from the effects of the external environment. Such environmental influences include, for example, atmospheric oxygen and light radiation, especially sunlight. The oxidizing effect of atmospheric oxygen can be counteracted, for example, by suitable antioxidants. Light stabilizers may be used to counteract the deleterious effects of light radiation.

The protective effects of some benzoic acids and their salts have been known for a long time. They are used inter alia in foods for microbiological stabilization in primarily acidic applications and as E210 (benzoic acid), E211 (sodium benzoate), E212 (potassium benzoate) and E213 (calcium benzoate). Are known. Various parabens (hydroxybenzoic acid esters) are also used, including E214 (ethyl p-hydroxybenzoate), E215 (ethyl sodium p-hydroxybenzoate), E218 (methyl p-hydroxybenzoate), and E219 (p-hydroxybenzoic acid ester). (BGBI. I 2000, 1537-1545). This substance class is also widely used in cosmetics for the purpose of improving (microbiological) stability.
Suitable stabilizers can also be taken from, for example, DE 29924656, DE 69917811, DE 69624799, EP 2952103 (EP 2952103) and DE 69518581.
According to one embodiment, the Yarrow fresh plant juice is concentrated at a temperature of <60°C.

Concentration may be carried out under normal pressure (1013 mbar) or under partially negative pressure, for example between 100 and 1000 mbar, preferably between 200 and 500 mbar. Preferably, the concentration of Yarrow fresh plant juice is carried out at a temperature of <55°C, more preferably <50°C, <45°C, <40°C, <35°C, <30°C, <25°C, even more preferably Performed at <10°C, <0°C, or <20°C. The combination of partial negative pressure and low temperature is particularly preferred since it is a gentle treatment of the concentrate.
According to one embodiment, the Yarrow fresh plant juice is concentrated by a concentration process selected from freeze drying, spray drying and reverse osmosis, or a combination thereof. These processes are well known in the art.

Reverse osmosis has been shown to be particularly advantageous for the production of the water-based extract/juice concentrates of the present invention because it is a gentle concentration of aqueous solutions. Reverse osmosis, also known as ultrafiltration, typically uses PAN (polyacrylonitrile), PES (polyethersulfone) with a NaCl rejection rate of ≧90%, preferably ≧95%, ≧97%, more preferably 99%. and/or PVDF (polyvinylidene difluoride) membranes for operating flow rates of 8 l/m ² /h to 34 l/m ² /h, preferably 8 l/m ² /h to 25 l/m ² /h, 8 l/m ² /h to 20 l/m ² /h pressure, more preferably 8 l/m ² /h to 15 l/m ² /h, pressure 15 to 50 bar, preferably 15 to 40 bar, more preferably 15 to 35 bar, and temperature ≦ It is carried out at 60°C, preferably ≦50°C, ≦40°C, more preferably ≦30°C.
It is also advantageous to protect these concentrates from microbial contamination. This can be achieved, for example, by lowering the pH value and/or by adding suitable preservatives as mentioned above.
Freeze-drying, also referred to as freeze-drying or sublimation drying, is an extremely gentle process, although cost-intensive and relatively complex. Freeze-drying is based on the physical process of sublimation: by this process ice crystals sublimate directly into the gaseous state without the appearance of an intermediate liquid phase. In this case, freeze-drying produces a solid that can be stored well without the addition of preservatives. Freeze-drying procedures can be taken, for example, from GB1447988 and DE19817177.

In spray drying, for example in a fluidized bed, the material to be dried is introduced into a hot gas stream by means of a vaporizer and is dried to a fine powder within a very short time (from a few seconds to a fraction of a second). Spray drying may optionally be carried out with the addition of the aforementioned carriers such as maltodextrins, cyclodextrins, etc. The advantage here is that it is an established method that can be performed cost-effectively. At higher temperatures, such as from 200 to 400°C, preferably from 250 to 270°C, only very short exposures, such as a few seconds, preferably less than 3 seconds or less than 1 second, are required. A solid is obtained which can be stored well without the addition of preservatives.
Yarrow fresh plant juice concentrate can preferably be obtained by the method of the invention.

According to one embodiment, a cosmetic composition, a pharmaceutical composition, a food composition or a food supplement is provided. The pharmaceutical composition, food composition or food supplement each comprises the Yarrow fresh plant juice concentrate of the present invention. The cosmetic composition comprises Yarrow fresh plant juice or Yarrow fresh plant juice concentrate of the present invention.
The concentrates of the invention have a wide range of applications in human cosmetics and care, in particular skin and hair care, but can also be used medicinally and in foods and food supplements.
Cosmetic compositions may in particular be dermocosmetic, haircosmetic, dermatological and hygiene compositions. In particular, the concentrates of the invention are used in skin and/or hair cosmetics.

The hair or skin care compositions or preparations of the invention are preferably in the form of emulsions, dispersions, suspensions, aqueous surfactant preparations, milks, lotions, creams, balms, ointments, gels, granules. , a powder, a stick preparation such as a lipstick, a foam, an aerosol or a spray. Such formulations are suitable for topical preparation. Oil-in-water emulsions and water-in-oil emulsions or microemulsions can be used as emulsions.
Generally, hair or skin cosmetic preparations are used for application to the skin or hair. "Topical preparation" means a preparation suitable for application to the skin, containing the active ingredient in finely dispersed form, eg, in a form that is absorbed through the skin. Suitable are, for example, aqueous and hydroalcoholic solutions, sprays, foams, foam aerosols, ointments, aqueous gels, O/W or W/O emulsions, microemulsions or cosmetic stick preparations.

Cosmetic compositions may include one (or several) carriers. Preferred carriers are water, gases, water-based liquids, oils, gels, emulsions or macroemulsions, dispersions or mixtures thereof. The described carrier shows good skin compatibility. Particularly advantageous for topical preparations are aqueous gels, emulsions or microemulsions. The carrier may also be in the form of a homogeneous formulation or an emulsion. Emulsions may be oil-in-water, water-in-oil or multiphase emulsions. These emulsions may be used in a wide range of consistencies, including liquid lotions (which may also be administered as sprays or aerosols), creamy lotions, light or heavy creams, and the like. Other suitable carriers include anhydrous liquid solvents such as oils and alcohols, water-based single phase liquid solvents (e.g. hydroalcoholic solvent systems), anhydrous solids and semi-solids (e.g. gels and sticks) and water-based gels. and foam types. Examples of suitable carriers and carrier systems within the framework of the invention are, for example, "Sun Products Formulary" Cosmetics & Toiletries, Vol. 105, p. 122-139 (December 1990); "Sun Products Formulary", Cosmetics & Toiletries, Vol. 102, p. 117-136 (March 1987); US Pat. No. 4,960,764, Figueroa et al. and U.S. Pat. No. 4,254,105, Fukuda et al. It can be picked up from.

The teachings of the present invention also include the use of the concentrates described herein in pharmaceutical compositions. This pharmaceutical composition may be used as a medicament for the treatment of individuals, preferably mammals, especially humans. Pharmaceutical compositions usually contain a concentrate of the invention and, if appropriate, a pharmaceutically acceptable excipient together with one or several other active substances.

These compositions may be administered, for example, orally and transdermally. Examples of suitable pharmaceutical formulations are powders, granules, tablets, troches, sachets, cachets, dragees, capsules such as hard and soft gelatin capsules, semi-solid dosage forms such as ointments, creams, hydrogels, pastes or plasters, etc. and liquid dosage forms such as solutions, emulsions, especially oil-in-water emulsions, and suspensions such as lotions.
In producing the compositions of the invention, the components or active ingredients used according to the invention are usually mixed or diluted with excipients. Excipients may be solid, semi-solid or liquid materials that serve as vehicles, carriers or mediums for the active ingredient contained in the concentrate. The content of active substances (of one or several active substances included at the same time according to the invention) may vary over a wide range.

Suitable excipients include lactose, glucose, sucrose, sorbitol, mannitol, starch, gum acacia, calcium phosphate, alginate, tragacanth, gelatin, calcium silicate, microcrystalline cellulose, polyvinylpyrrolidone, cellulose, water, syrup and methylcellulose. is included. Additionally, the formulation includes pharmaceutically acceptable carriers or common excipients, such as lubricants such as tallow, magnesium stearate and mineral oil; wetting agents; emulsifying and suspending agents; methyl hydroxybenzoate and Preservatives such as propyl; antioxidants; anti-irritants; chelating agents; coating aids; emulsion stabilizers; film-forming agents; gelling agents; odor masking agents; flavor correctors; resins; hydrocolloids; solvents; Solubilizing agents; neutralizing agents; penetration enhancers; pigments; quaternary ammonium compounds; fatliquing and superfatting agents; ointments, creams or oily bases; silicone derivatives; spreading aids; stabilizers; bactericidal agents; Tablet adjuvants such as binders, fillers, lubricants, disintegrants or coating agents; propellants; desiccants; opacifiers; thickeners; waxes; plasticizers; white oils. The design in this respect can be found in, for example, Fiedler, H. P., Lexikon der Hilfsstoffe fur Pharmazie, Kosmetik und angrenzende Gebiete, 4th edition, Aulendorf: ECV-Editio-Kantor-Verlag, 1996, or Hager's Handbuch der Pharmazeutischen Praxis, Springer Verlag, Heidelberg. As indicated, based on the knowledge of a person skilled in the art.

Within the framework of the invention, it is possible to combine fresh plant juices or concentrates according to the invention or in accordance with the invention with, for example, abrasives, anti-acne and sebum-reducing agents, anti-aging agents, antibacterial agents, anti-cellulite agents. , anti-dandruff agents, anti-inflammatory agents, anti-irritants, anti-irritants (anti-inflammatory, anti-irritant and anti-irritating agents), anti-microbial agents, antioxidants, astringents, preservatives, antistatic agents, binders, buffers , carriers, chelating agents, cell activators, cleansing agents, care agents, depilatory agents, surfactants, deodorants and antiperspirants, plasticizers, emulsifiers, enzymes, essential oils, insect repellents, fibers, film-forming agents, fixatives foaming agents, foam stabilizers, antifoaming agents, foaming accelerators, fungicides, gelling agents and gel forming agents, hair care agents, hair shaping agents, hair straightening agents, moisture regulators (moisturizing, moisturizing) and/or humectants), osmotic pressure regulators, compatible solutes, bleaching agents, enhancers, stain removers, optical brighteners, impregnators, antifouling agents, friction reducers, lubricants, moisturizing creams. , ointments, clouding agents, plasticizers, opacifiers, polishes, brighteners, polymers, powders, proteins and protein hydrolysates, fatliquors, abrasives, skin soothing agents, skin cleansing agents, skin care agents, preferably is a skin repair agent, skin whitening agent, skin protection agent, emollient, skin cooling agent, preferably a skin warming agent as described in WO 2005/123101, containing cholesterol and/or fatty acid and/or ceramide and/or pseudoceramide; UV absorbers and UV filters, preferably those described in WO 2005/123101, benzylidene-β-dicarbonyl compounds, α-benzoylcinnamic nitrile, AhR receptor antagonists, detergents, fabric softeners, suspending agents, Skin tanning agents, thickeners, vitamins, oils, waxes and lipids, phospholipids, fatty acids (saturated, mono- or polyunsaturated, alpha-hydroxy acids, polyhydroxy fatty acids), plasticizers, dyes and color protectants. and pigments, anticorrosive agents, fragrances and flavors, and fragrances, preferably S. Arctander, Perfume and Flavor Chemicals, self-published, Montclair, NJ, 1969 and Surburg, Panten, Common Fragrance and Flavor Materials, 5th Edition, Wiley- VCH, Weinheim 2006, surfactants, animal extracts, yeast extracts, algae or microalgae extracts, electrolytes, liquefaction agents, organic solvents, hair growth regulators (promoting or inhibiting hair growth) ) and (other) (active) substances selected from the group consisting of silicones and silicone derivatives, preferably one or several skin cooling agents and/or one or several UV absorbers or UV filters. Their use together is generally possible and usually advantageous.
The compositions of the invention may therefore also contain (further) cosmetically and/or dermatologically and/or pharmacologically active agents in addition to the customary additives or excipients.

Suitable cosmetically and/or dermatologically active agents are, for example, colorants, skin and hair dyes, tinting agents, tanning agents, bleaching agents, keratin-hardening substances, antimicrobial agents, light filtering agents, hyperemic agents. hyperemising substances, keratolytic and keratinogenic substances, antidandruff agents, anti-inflammatory agents, keratinizing substances, substances active as antioxidants or radical scavengers, skin moisturizing or moisturizing substances, fattening agents, antierythematous or antiallergic active agents, branched fatty acids such as 18-methyleicosanoic acid, and mixtures thereof.

Artificial skin tanning agents suitable for tanning the skin without natural or artificial irradiation with UV light; these are, for example, dihydroxyacetone, alloxan and walnut shell extract. Suitable keratin-hardening substances are agents such as those commonly used in antiperspirants, such as potassium aluminum sulphate, aluminum chlorohydroxyl, aluminum lactate, and the like.

Antimicrobial agents used to prevent or inhibit the growth of microorganisms. Antimicrobial agents therefore act as preservatives and as deodorants, reducing the production or intensity of body odors. Antimicrobial agents include, for example, common preservatives known to those skilled in the art, such as p-hydroxybenzoic acid esters, imidazolidinyl ureas, formaldehyde, sorbic acid, benzoic acid, salicylic acid, and the like. Such deodorizing substances are, for example, zinc ricinoleate, triclosan, undecylenic acid alkylolamide, citric acid triethyl ester, chlorhexidine, and the like.

The person skilled in the art is familiar with excipients and additives suitable for the production of hair and skin cosmetic preparations, and is familiar with the excipients and additives suitable for the production of hair and skin cosmetic preparations, and is familiar with cosmetic manuals, such as Schrader, Grundlagen und Rezepturen der Kosmetika, Huthig Verlag, Heidelberg, 1989, ISBN 3-7785-1491-1. Excipients and additives are preferably cosmetically and/or pharmaceutically acceptable excipients. Pharmaceutically acceptable are excipients known to be applicable in pharmaceuticals, food technology and related fields, especially those in the relevant pharmacopeias (e.g. DAB, Ph. Eur., BP, NF). ), as well as other excipients whose properties are compatible with physiological applications.

Suitable excipients include lubricants, wetting agents, emulsifying and suspending agents, preservatives, antioxidants, anti-irritants, chelating agents, emulsion stabilizers, film-forming agents, gelling agents, odor Masking agents, hydrocolloids, solvents, solubilizers, neutralizing agents, penetration enhancers, pigments, quaternary ammonium compounds, fatliquing and superfatting agents, ointments, creams or oil bases, silicone derivatives, stabilizers, They may be disinfectants, propellants, desiccants, opacifiers, thickeners, waxes, plasticizers and white oils.
Further suitable additives are perfume oils, hair polymers, hair and skin conditioners, graft polymers, water-soluble or dispersible silicone-containing polymers, photoprotectants, bleaching agents, care agents, dyes, tinting agents, tanning agents, dyes, selected from viscosity improvers, humectants, fatliquors, collagen, protein hydrolysates, lipids, antioxidants, defoamers, antistatic agents, emollients, plasticizers, peroxide decomposers.
As examples of suitable excipients and additives, mention may be made of antioxidants, peroxide decomposers, thickeners and the preservatives mentioned above.

Peroxide decomposers are compounds that chemically decompose peroxides, especially lipid peroxides. Examples include pyridine-2-thiol-3-carboxylic acid, 2-methoxy-pyrimidinolcarboxylic acid, 2-methoxy-pyridinecarboxylic acid, 2-dimethylamino-pyrimidinolcarboxylic acid, 2-dimethylamino-pyridine Contains carboxylic acid.
Examples of thickeners are crosslinked polyacrylic acids and their derivatives, polysaccharides and their derivatives such as xanthan gum, agar agar, alginates or tylose, cellulose derivatives such as carboxymethylcellulose or hydroxycarboxymethylcellulose, fatty alcohols, monoglycerides and fatty acids, polyvinyl alcohol and polyvinylpyrrolidone. In particular, nonionic thickeners are used.

In addition to preservatives, other antibacterial agents can also be used and incorporated into the compositions of the present invention. Preferred substances are, for example, 2,4,4'-trichloro-2'-hydroxydiphenyl ether (Irgasan), 1,6-di-(4-chlorophenylbiguanide)-hexane (chlorhexidine), 3,4,4'- Trichlorocarbanilide, quaternary ammonium compounds, clove oil, mint oil, thyme oil, triethyl citrate, farnesol (3,7,11-trimethyl-2,6,10-dodecatrien-1-ol) and DE3740186, DE3938140, DE4204321, DE4229707, DE4309372, DE4411664, DE19541967, DE19543695, DE19543696, DE19547160, DE19502108, DE19602110, DE19602 111, DE19631003, DE19631004 and DE19634019 and the agents or combinations of agents described in DE4229737, DE4237081, DE4324219, DE4429467, DE4423410 and DE19516705. be. Sodium bicarbonate can advantageously be used. Antimicrobial polypeptides can also be used.

Light filtering agents may also be included. These agents absorb UV radiation in the UV-B and/or UV-A range. Suitable UV filters are suitable, for example, in which the aryl groups each carry at least one substituent, preferably selected from hydroxy, alkoxy, in particular methoxy, alkoxycarbonyl, in particular methoxycarbonyl and ethoxycarbonyl, and mixtures thereof. 2,4,6-triaryl-1,3,5-triazine. Also suitable are p-aminobenzoic acid esters, cinnamic acid esters, benzophenones, camphor derivatives and pigments that screen UV radiation, such as titanium dioxide, talcum and zinc oxide.
Any UV-A and UV-B filter material can be considered a UV filter material. Examples that can be mentioned are:

The cosmetic and dermatological preparations of the invention may also advantageously contain, for example, zinc oxide (ZnO), titanium oxide (TiO ₂ ), iron oxides (e.g. Fe ₂ O ₃ ), zirconium oxide (ZrO ₂ ), silicon oxide (SiO ₂ ), manganese oxide (e.g. MnO), aluminum oxide (AI ₂ O ₃ ), cerium oxide (e.g. Ce ₂ O ₃ ), mixed oxides of such metals and mixtures of such oxides, inorganic pigments and/or other metal compounds based on metal oxides may be included.
Suitable hyperemic substances may also be included in the cosmetic or pharmaceutical composition. Hyperemic substances stimulate blood circulation in the skin. Examples are mountain pine extract, lavender extract, rosemary extract, juniper berry extract, horse chestnut extract, birch leaf extract, hayflower extract, ethyl acetate, camphor, menthol, peppermint oil, rosemary extract. , eucalyptus oil, etc.
Keratolytic and keratinogenic substances may also be included. Examples of such substances include salicylic acid, calcium thioglycolate, thioglycolic acid and their salts, sulfur, and the like. Suitable anti-dandruff agents include sulfur, sulfur polyethylene glycol, sorbitan monooleate, sulfur uricinol polyethoxylate, zinc pyrithione, aluminum pyrithione, and the like.
Suitable anti-inflammatory agents to soothe skin irritation are, for example, allantoin, bizabolol, dragosantol, chamomile extract, panthenol, and the like.

Cosmetic or pharmaceutically acceptable polymers such as cationic, amphoteric and neutral polymers. Suitable polymers are, for example, cationic polymers with the name polyquaternium according to INCI, such as copolymers of vinylpyrrolidone/N-vinylimidazolium salts (Luviquat FC, Luviquat HM, Luviquat MS, Luviquat C are), sulfuric acid Copolymer of N-vinylpyrrolidone/dimethylaminoethyl methacrylate quaternized with diethyl (Luviquat PQ 11), copolymer of N-vinylcaprolactam/N-vinylpyrrolidone/N-vinylimidazolium salt (Luviquat E Hold), cationic These are cellulose derivatives (polyquaternium-4 and -10), acrylamide copolymers (polyquaternium-7) and chitosan.

Suitable cationic (quaternized) polymers are also merquat (a polymer based on dimethyldiallylammonium chloride), gafquat (a polymer formed by the reaction of polyvinylpyrrolidone with a quaternary ammonium compound), polymer JR (hydroxyethylcellulose with cationic groups) and plant-based cationic polymers, such as guar polymers such as the Jaguar brand from Rhodia.

Other suitable polymers are also polyvinylpyrrolidone, copolymers of N-vinylpyrrolidone and vinyl acetate and/or vinyl propionate, polysiloxanes, polyvinylcaprolactam and other copolymers with N-vinylpyrrolidone, polyethyleneimine and their salts. , polyvinylamine and their salts, cellulose derivatives, polyaspartates and their derivatives, and other neutral polymers. These include, for example, Luviflex® Swing (a partially saponified copolymer of polyvinyl acetate and polyethylene glycol, BASF).
Suitable polymers are also non-ionic, water-soluble or water-dispersible polymers or oligomers, for example polyvinylcaprolactam, such as Luviskol® Plus (BASF), or polyvinylpyrrolidone and their copolymers, especially vinyl acetate, such as Copolymers with esters, such as B. Luviskol® VA37 (BASF), polyamides such as those based on itaconic acid and aliphatic diamines, such as those described in DE-A-4333238.

Suitable polymers are also amphoteric or dipolar polymers, such as octylacrylamide/methyl methacrylate/tert-butylaminoethyl methacrylate-hydroxypropyl-methacrylate copolymers available under the name Amphomer (National Starch), and for example DE 3929973, DE 2150557 , DE2817369 and DE3708451. Acrylamidopropyltrimethylammonium chloride/acrylic acid or methacrylic acid copolymers and their alkali and ammonium salts are preferred dipolar polymers. Further suitable dipolar polymers are the methacroylethyl betaine/methacrylate copolymers sold under the name Amersette (AMERCHOL) and the copolymers of hydroxyethyl methacrylate, methyl methacrylate, N,N-dimethylaminoethyl methacrylate and acrylic acid (Jordapon). (D)). Suitable polymers are also non-ionic, siloxane-containing, water-soluble or water-dispersible polymers, for example polyether siloxanes such as Tegopren® (Goldschmidt) or Besi (Wacker).
A further object of the invention relates to foods or food supplements comprising the concentrates of the invention.

The products prepared are food products of any kind insofar as they are food products to which the concentrate is directly added. For example, bakery products, alcoholic or non-alcoholic beverages, fruit-based lemonades, isotonic (carbonated) drinks, soft drinks (carbonated), nectars, spritzers, fruit and vegetable juices, fruit or vegetable juice preparations and dairy products. can be mentioned. Preferably, these are food products that do not require heating during preparation.
If the product is a food supplement, it is generally used without any other additives other than the pure packaging material. Macrocapsules or microcapsules are a preferred application form. Macrocapsules are preferably spray-dried products consisting of gelatin or containing polysaccharides or dextrins as a base.
According to one embodiment, the cosmetic or pharmaceutical composition further comprises 0.01-10% by weight of skin soothing agents and/or antioxidants.
Examples of suitable skin soothing or emollient agents for topical compositions include bisabolol, allantoin, menthol, sucrose, centella extract, licorice extract, farnesol, ruscus extract, mallow extract, jasmine extract, rose Plant extracts containing maricic acid and rosemaric acid, oat extract, ginger extract, [6]-paradol, Hamamelis extract, calendula extract, arnica extract, echinacea extract, hydrogenated polyisobutene, C12-C15 benzoin Acid alcohols, isopropyl myristate, mineral oil, lanolin and lanolin derivatives, triglycerides such as coconut oil, cetostearyl alcohol, cetyl alcohol, isopropyl palmitate, caprylic/capric triglyceride, PPG-2 myristyl ether propionate, dimethicone, Includes methicone, petrolatum and other skin soothing agents well known to those skilled in the art.

Antioxidants are preferably amino acids (e.g. glycine, histidine, tyrosine, tryptophan) and their derivatives, imidazoles (e.g. urocanic acid) and their derivatives, peptides such as D,L-carnosine, D-carnosine, L-carnosine and their derivatives. derivatives (e.g. anserine), carotenoids, carotenes (e.g. β-carotene, lycopene) and their derivatives, chlorogenic acid and its derivatives, lipoic acid and its derivatives (e.g. dihydrolipoic acid), aurothioglucose, propylthiouracil and others. Thiols (e.g. thiorodoxin, glutathione, cysteine, cystine, cystamine and their glycosyl, N-acetyl, methyl, ethyl, propyl, amyl, butyl and lauryl, palmitoyl, oleyl, y-linoleyl, cholesteryl and glyceryl esters) and their salts , dilaurylthiodipropionate, distearylthiodipropionate, thiodipropionic acid and its derivatives (esters, ethers, peptides, lipids, nucleotides, nucleosides and salts) and sulfoximine compounds (e.g. buthionine sulfoximine, homocysteine). sulfoximine, buthionine sulfone, penta-, hexa-, heptathionine sulfoximine), especially at very low compatible doses (e.g. in the pmol to μmol/kg range), further (metal)-chelating agents (e.g. d - hydroxy fatty acids, palmitic acid, phytic acid, lactoferrin), o-hydroxy acids (e.g. citric acid, lactic acid, malic acid), humic acids, bile acids, bile extracts, bilirubin, biliverdin, EDTA and its derivatives, unsaturated fatty acids and its derivatives (e.g. v-linolenic acid, linoleic acid, oleic acid), folic acid and its derivatives, ubiquinone and ubiquinol (ubiquinolv) and its derivatives, vitamin C and its derivatives (e.g. sodium ascorbate, ascorbyl palmitate, ascorbyl phosphate). Mg, ascorbyl acetate), tocopherols and their derivatives (e.g. vitamin E acetate, tocotrienols), vitamin A and derivatives (vitamin A palmitate) and coniferyl benzoate of benzoic resin, rutic acid and its derivatives, o-glycosylrutin, ferulic acid, Furfurylidenglucitol, carnosine, butylated hydroxytoluene, butylated hydroxyanisole, nordihydroguaiac resin acid, nordihydroguaiaretic acid, trihydroxybutyrophenone, [6]-paradol, 4-hydroxyacetophenone, uric acid and its derivatives, Selected from mannose and its derivatives, zinc and its derivatives (eg ZnO, ZnSO ₄ ), selenium and its derivatives (eg selenomethionine), stilbene and its derivatives (eg stilbene oxide, trans-stilbene oxide).
According to one embodiment, the use of Yarrow is provided for stimulating the expression of heat shock proteins (HSPs) and/or antimicrobial peptides (AMPs) in skin cells.

Human skin is a boundary organ, providing protection against environmental influences, among other things. Human skin is constantly exposed to numerous potentially dangerous microorganisms. Despite this threat from microorganisms, the skin is extremely resistant to infection. Several studies conducted in the last decade have demonstrated a chemical defense system in the skin based on the production of antimicrobial peptides and proteins (AMPs). AMPs represent a diverse group of small molecules (12-100 amino acid residues) that constitute a major effector system of innate immunity. These provide the first line of defense against pathogens. AMPs produced in response to a hazard can be quickly primed against a wide range of microorganisms, such as bacteria, fungi, viruses or protozoa, with a broad spectrum of effective antimicrobial activity. AMP is found in a variety of exposed tissues or surfaces such as the skin, eyes, ears, mouth, respiratory tract, lungs, intestines, and urinary tract. In human skin, AMP can be produced structurally by resident skin cells, by infiltrating immune cells or in response to risks such as infection, trauma, wound healing or chronic inflammation. AMP is produced in human skin primarily by keratinocytes, neutrophils, sebaceous gland cells or sweat glands. In several diseases of human skin, there is a correlation between disease severity and the level of AMP production. Skin lesions in atopic dermatitis patients show reduced defensin and cathelicidin LL-37. Increased AMP levels are also associated with burns and chronic wounds. In contrast, overexpression of AMP can lead to increased protection against skin infections, as seen in patients with psoriasis, rosacea, and inflammatory skin infections that rarely lead to superinfections. Defensins, including the α and β families, are one of the largest and most studied AMP families in mammals. They are produced by a variety of skin- and bone marrow-derived cells, exhibit a broad spectrum of antimicrobial activity against Gram-positive and Gram-negative bacteria, viruses, fungi and some protozoa, and are important components of the innate immune system. It is. Beta-defensins are cationic peptides with antimicrobial activity that protect epithelial surfaces, including the skin, gastrointestinal tract, urinary tract, and respiratory tract. Human β-defensin 1 peptide (hBD-1) is encoded by the DEFB1 locus and is active against Gram-positive and Gram-negative bacteria. After reduction of the disulfide bridges, hBD-1 becomes an effective AMP against the opportunistic pathogenic fungus Candida albicans. Shows synergistic effects with LL-37 or lysozyme against S. aureus and E. coli.

The S100 protein is a low molecular weight cationic protein characterized by two calcium-binding EF hand motifs. S100 is involved in numerous cellular processes, such as calcium-dependent cell signaling, cell proliferation, and defense against microorganisms. S100 calcium binding protein A8 (S100A8) is a protein encoded by the S100A8 gene in humans. S100A8 (calgranulin A) and S100A9 (calgranulin B) form an antimicrobial heterodimeric complex, also known as calprotectin, in epidermal keratinocytes. The S100A8/S100A9 complex can also be used for, for example, E. coli, Klebsiella spp., Staphylococcus aureus, S. epidermis, Capnocytophaga sputigena, and Borrelia burgdorferi. It has been shown to have antibacterial activity against bacteria such as Borrelia burgdorferi as well as antifungal activity against the fungus Candida albicans.

Heat shock proteins (HSPs) are molecular chaperones that prevent cell death. Organisms and cells respond to various stress conditions, such as environmental, metabolic and pathophysiological stress, by selectively upregulating HSPs. HSPs are confirmed by increased expression after heat shock (usually at a temperature 3 to 5° C. higher than room temperature for 1 hour or more). The presumption that HSPs protect cells from heat damage is supported by the following facts: 1) HSP expression occurs precisely in parallel with the development and decline of heat tolerance (heat death resistance); 2) HSP mutations or inactivation impairs the cell's ability to survive high temperatures; 3) HSP overexpression can often enhance the cell's ability to withstand high temperatures. Induction of heat shock protein HSP70 in human keratinocytes and NIH/3T3 fibroblasts by cinnamic acid derivatives, especially chlorogenic acid, has been described, for example, in US Pat. No. 9,265,743.

These proteins are classified into six major families based on molecular weight: Hsp100, Hsp90, Hsp70, Hsp60, Hsp40 and small heat shock proteins (sHsp). sHsp has a subunit molecular weight of 12-43 kDa. The ability to prevent protein and polypeptide aggregation, especially under stress conditions that lead to unfolding of cellular proteins, is the most important function of many sHSPs. Human sHSPs have different characteristics with respect to their heat-inducible expression, tissue and subcellular localization, structure, substrate selectivity and function. Because of this difference, human sHSPs have different abilities to prevent acute and different types of chronic (disease-related) stress.
HSP27 belongs to small heat shock proteins (sHSPs). HSP27 is an ATP-independent molecular chaperone that prevents stress-induced protein aggregation. Hsp27 is found in intact skin, primarily in the stratum granulosum and stratum spinosum of the epidermis.
According to one embodiment, there is provided the use of yarrow to increase heat tolerance of the skin.

Skin thermotolerance involves an induced phenomenon in which cells become resistant to otherwise damaging or lethal heat stress following heat stress. Maytin E. et al. (J. Invest. Dermatol 1990;95: 635-42; J. Biol Chem. 1992; 267: 231 89-96; J. Invest Dermatol 1995; 104 [4]: 448-55, Farage MA. Textbook of Aging Skin. Springer-Verlag Berlin Heidelberg 2010), heat stress on human keratinocytes not only leads to increased heat tolerance and heat shock protein synthesis, but also to other stress stimuli such as heavy metals and hypoxia. It can be seen that it also leads to insensitivity to UVB and, surprisingly, also to resistance to UVB-induced damage.
According to one embodiment, Yarrow is used as Yarrow fresh plant juice or as a cosmetic composition in use according to the invention.
According to one embodiment, when used according to the invention, the dose of Yarrow fresh plant juice concentrate in the cosmetic composition is from 0.0001 to 10% by weight relative to 100% by weight of the cosmetic composition. %.
Preferably, the dose of Yarrow fresh plant juice concentrate in cosmetic compositions, especially cosmetic compositions for skin and hair cleansing and care, is from 0.001 to 5% by weight, more preferably from 0.001 to 5% by weight. 0.005 to 3% by mass.
According to one embodiment, the pharmaceutical composition of the invention is used as a medicament.
Pharmaceutical compositions of the invention may also be used in cancer prevention and treatment of skin diseases.

In diseases such as atopic dermatitis, actinic keratoses, skin cancer precursors, psoriasis, rosacea and other skin diseases characterized by barrier damage and chronic inflammation, the synthesis of heat shock proteins in relevant skin areas is reduced. However, skin repair mechanisms are known to be disrupted. A disturbance occurs in the controlled apoptosis of keratinocytes and the immune defense is weakened. In parallel with these processes, inflammatory enzymes such as matrix metalloproteases are increasingly formed. Skin aging and inflammation are characterized by the fact that the skin's repair mechanisms are disturbed and weakened, and inflammatory mediators are increasingly released.

In particular, the pharmaceutical compositions of the invention can be used within the framework of cancer therapy to avoid and/or reduce skin damage. This use of the pharmaceutical composition of the invention is based on the discovered mechanism of action of Yarrow, in particular the components of Yarrow that increase the heat tolerance of the skin. This effect is thought to be due to the expression of heat shock proteins in skin cells. This effect can be used to protect healthy skin cells from the effects of drug therapy and/or radiation in the context of cancer treatment, particularly radiation therapy for skin cancer. Yarrow's antibacterial properties also support this protective effect on human skin.
According to one embodiment, when Yarrow is used according to the invention or the pharmaceutical composition is used as a medicament according to the invention, topical application to the skin and/or hair is carried out.

In the context of the present invention, the term "have" or "having" refers to an open enumeration, including other components or steps in addition to the explicitly mentioned components or steps. This does not exclude steps. In the context of the present invention, if a composition is described using the expressions "have" or "having", it means that the composition consists of the specified components or has the specified configuration. It clearly includes what becomes basic from the element.
In the context of the present invention, the term "consisting of" refers to an exhaustive enumeration and excludes any other components or steps apart from the explicitly mentioned components or steps.
In the context of the present invention, the term "essentially consisting of" refers to a partially exhaustive list of components that, in addition to the specified components, do not substantially change the characteristics of the composition. or only those additional components present in amounts that do not substantially alter the characteristics of the composition.

Further features and advantages of the invention result from the following description of preferred embodiments.

All specifications expressed in % in the examples refer to specifications in % by weight, unless explicitly stated otherwise.

(Example 1)
Production of Achillea millefollium fresh plant press concentrate by freeze-drying 100 ml of Achillea millefollium fresh plant press (Schoenenberger), produced from a flowering herb grown in Germany, was frozen and then Freeze dry. 5.3 g of dried juice 1a are obtained as a brown-green solid and its composition is analyzed:

結果は、セイヨウノコギリソウ（Ａｃｈｉｌｌｅａ ｍｉｌｌｅｆｏｌｌｉｕｍ）フレッシュ植物圧搾汁（Ｓｃｈｏｅｎｅｎｂｅｒｇｅｒ社）の４バッチは、平均４．７±０．４ｇのセイヨウノコギリソウフレッシュ植物圧搾汁濃縮物を与えた。
フリーズドライしたセイヨウノコギリソウフレッシュ植物圧搾汁濃縮物は、平均でわずか６．６±１．０％の水、９．６±１．３％のモノカフェオイルキナ酸の総和、４．５±１．０％のジカフェオイルキナ酸の総和および０．３±０．１％のルチンを含む。 Three additional batches of Achillea millefolium fresh plant juice (Schoenenberger), 100 ml each, are frozen and subsequently freeze-dried. The resulting dried juices 1b-1d are weighed and analyzed for total mono- and dicaffeoylquinic acids and rutin:

The results showed that four batches of Achillea millefolium fresh plant juice (Schoenenberger) gave an average of 4.7±0.4 g of Achillea millefolium fresh plant juice concentrate.
Freeze-dried Yarrow fresh plant juice concentrate contains on average only 6.6±1.0% water, 9.6±1.3% total monocaffeoylquinic acid, 4.5±1. Contains 0% total dicaffeoylquinic acid and 0.3±0.1% rutin.

(Example 2)
Preparation of Yarrow Fresh Plant Juice Concentrate by Spray Drying 1 l of Yarrow Fresh Plant Juice (Schoenenberger, dry matter content 5.3%) is mixed with 150 g of maltodextrin DE 17-20 and spray dried. The result is a beige free-flowing powder consisting of 75% maltodextrin and 25% dry Yarrow fresh plant juice. The spray-dried concentrate is analyzed for total mono- and dicaffeoylquinic acids and rutin:

分析結果は、成分が噴霧乾燥の間に変化せずに残存し、分解は起こらなかったことを示す。

Analytical results show that the components remained unchanged during spray drying and no decomposition occurred.

(Example 3)
Effect of Yarrow Fresh Plant Juice Concentrate on Gene Expression of Heat Shock Proteins in Skin Cells Neonatal human epidermal keratinocytes (nHEK) were seeded in 6-well microtiter plates at a density of 0.2 x ¹⁰ cells/cavity. , cultured in EpiLife medium. After an incubation period of 24 hours, the Yarrow fresh plant juice concentrate obtained in Example 1 is added to the EpiLife at a concentration of 0.005% by weight and incubated for 24 hours.

Isolation and purification of mRNA is performed using Qiagen's RNeasy® Mini Kit. Elution of mRNA from the column is performed using 50 μl of RNase-free water. Quantification and purity determination of isolated RNA is performed spectrophotometrically. Purity is assessed by absorbance ratios E260/E280 and E260/E230. Transcription of RNA into cDNA is performed according to the manufacturer's instructions (RNA-to-cDNA Kit, Applied Biosystems). The amount transferred is 0.5-1 μg per 6 wells. Transferred samples are immediately processed by PCR or stored at -20°C until the experiment is continued.

In the next step, qRT-PCR is performed. For qRT-PCR, cDNA is thawed and mixed with TaqMan® Fast Universal PCR Master Mix (2×) (Life Technologies). 96-well TaqMan® plates (Life Technologies, Darmstadt) can be individually equipped with the desired primers. Pipette a volume of 10 μL of sample into each well of a 96-well array plate, carefully seal the wells hermetically with adhesive film (MicroAmp®), and centrifuge. Gene expression analysis is performed on a StepOne Plus Fast Real-Time PCR machine (Applied Biosystems). After the heating step, the device automatically performs the cycles shown in Table 5 sequentially.

Measurements are exported to MS Office Excel for evaluation. Relative gene expression is calculated according to the ΔΔCT method. In the first step of calculation, the ΔCT value is calculated for each sample by subtracting the CT value of the reference gene (gene HRPT) from the CT value of the gene to be tested.
ΔCT value _{target gene} = CT value _{target gene} - CT value _{reference gene (HTRP gene)}
After standardization, the ΔCT value of the control sample (untreated) is subtracted from the ΔCT value of the treated sample (PS applied).
ΔΔCT value _{target gene} = ΔCT value _treatment - ΔCT value _control
In the final step, the relative expression difference (relative quantification value (RQ value)) between the stimulated sample (PS applied) and the control is calculated. Relative gene expression (RQ value) = 2 ^-ΔΔCT
RQ values of >2.5 are considered relative induction of the gene.

結果は、セイヨウノコギリソウフレッシュ植物圧搾汁が、非常に低い試験濃度において熱ショックタンパク質ＨＳＰ２７の遺伝子発現を非常に効果的に上方制御するが、ＨＳＰ７０には効果を及ぼさないことを示す。

The results show that Yarrow fresh plant juice very effectively upregulates the gene expression of heat shock protein HSP27, but has no effect on HSP70 at very low tested concentrations.

(Example 4)
Effect of Yarrow Fresh Plant Juice Concentrate on Gene Expression of AMP in Skin Cells HaCaT cells are seeded in 6-well microtiter plates at a density of 0.5 x ¹⁰ cells/well and cultured in EpiLife medium. .
After an incubation period of 2 days, the Yarrow fresh plant juice concentrate obtained in Example 1 is added to the EpiLife at a concentration of 0.005% by weight and incubated for 24 hours.
Isolation and purification of mRNA is performed using Qiagen's RNeasy® Mini Kit. Elution of mRNA from the column is performed using 50 μl of RNase-free water. Quantification and purity determination of isolated RNA is performed spectrophotometrically. Purity is assessed by absorbance ratios E260/E280 and E260/E230.
Transcription of RNA into cDNA is performed according to the manufacturer's instructions (RNA-to-cDNA Kit, Applied Biosystems). The amount transferred is 0.5-1 μg per 6 wells. Transferred samples are immediately processed by PCR or stored at -20°C until the experiment is continued.

In the next step, qRT-PCR is performed. For qRT-PCR, cDNA is thawed and mixed with TaqMan® Fast Universal PCR Master Mix (2×) (Life Technologies). 96-well TaqMan® plates (Life Technologies, Darmstadt) can be individually equipped with the desired primers. Pipette a volume of 10 μL of sample into each well of a 96-well array plate, carefully seal the wells hermetically with adhesive film (MicroAmp®), and centrifuge again for 1 minute. Gene expression analysis is performed on a StepOne Plus Fast Real-Time PCR machine (Applied Biosystems). After the heating step, the device automatically performs the cycles shown in Table 8 in sequence.

Measurements are exported to MS Office Excel for evaluation. Relative gene expression is calculated according to the ΔΔCT method. In the first step of calculation, the ΔCT value is calculated for each sample by subtracting the CT value of the reference gene (gene HRPT) from the CT value of the gene to be tested.
ΔCT value _{target gene} = CT value _{target gene} - CT value _{reference gene (HTRP gene)}
After standardization, the ΔCT value of the control sample (untreated) is subtracted from the ΔCT value of the treated sample (PS applied).
ΔΔCT value _{target gene} = ΔCT value _treatment - ΔCT value _control
In the final step, the relative expression difference (relative quantification value (RQ value)) between the stimulated sample (PS applied) and the control is calculated.
Relative gene expression (RQ value) = 2 ^-ΔΔCT
RQ values of >2.5 are considered relative induction of the gene.

結果は、セイヨウノコギリソウフレッシュ植物圧搾汁が、非常に低い試験濃度において、抗菌ペプチドβ－デフェンシン１およびＳ１００カルシウム結合タンパク質Ａ８の遺伝子発現を非常に効果的に上方制御することを示す。

The results show that Yarrow fresh plant juice very effectively upregulates the gene expression of the antimicrobial peptide β-defensin 1 and S100 calcium binding protein A8 at very low tested concentrations.

(Example 5)
Prescription example 1 = Soothing balm for skin 2 = Colored anti-aging balm, SPF15
3 = After sun moisturizing spray O/W
4=Night cream W/O
5=Facial Cleansing Gel 6=Aftershave Hydrogel 7=Anti-dandruff Hair Shampoo 8=Antiperspirant Pump Spray 9=Day Care Fluid O/W for Skin Lightening
10 = Barrier function recovery cream O/W
11 = Sun protection lotion SPF24 (UVA/UVB balance)
In formulation examples 1 to 11, the two perfume oils PFO1 and PFO2 described below are used as perfumes, respectively (DPG = dipropylene glycol).

Claims (13)

Based on the total weight of Yarrow fresh plant juice concentrate containing one or more dicaffeoylquinic acids:
10 to 100% by mass of yarrow fresh plant pressed juice dry residue,
Yarrow fresh plant press, lyophilized or spray dried, for topical application to the skin and/or hair, comprising or consisting of 0 to 10 % by weight of water and 0 to 90% by weight of carrier juice concentrate. The dicaffeoylquinic acid or one or more or all of the dicaffeoylquinic acids is 1,5-dicaffeoylquinic acid, 3,4-dicaffeoylquinic acid, 3,5-dicaffeoylquinic acid. and 4,5-dicaffeoylquinic acid, and 4,5-dicaffeoylquinic acid. The carrier is a solid carrier selected from the group consisting of maltodextrin, dextrin and cyclodextrin, and/or glycerol, propylene glycol, butylene glycol, 1,3-propanediol, 1,2-pentanediol, 1,2- Yarrow fresh plant juice concentrate according to claim 1 or 2, wherein the liquid carrier is selected from the group consisting of hexanediol and 1,2-octanediol. Yarrow fresh plant juice concentrate according to any one of claims 1 to 3, wherein the Yarrow fresh plant juice concentrate further comprises a preservative and/or a stabilizing agent. Yarrow fresh plant press concentrate according to any one of claims 1 to 4, which is a spray-dried product. preparing a Yarrow fresh plant press; and spray drying the Yarrow fresh plant press;
A method for producing a yarrow fresh plant press concentrate according to any one of claims 1 to 5, comprising or consisting of the steps of: Cosmetic composition for topical application to the skin and/or hair, comprising a Yarrow fresh plant juice concentrate according to any one of claims 1 to 5. Pharmaceutical composition for topical application to the skin and/or hair, comprising a Yarrow fresh plant juice concentrate according to any one of claims 1 to 5. Cosmetic composition according to claim 7, further comprising 0.01 to 10% by weight of skin soothing agents and/or antioxidants . Pharmaceutical composition according to claim 8, further comprising 0.01 to 10% by weight of a skin soothing agent and/or an antioxidant. Yarrow fresh plant juice concentrate according to any one of claims 1 to 5 for stimulating the expression of heat shock proteins (HSPs) and/or antimicrobial peptides (AMPs) in skin cells. Yarrow fresh plant juice concentrate according to any one of claims 1 to 5 for increasing the heat tolerance of the skin. Cosmetic composition according to claim 7 or 9 , comprising Yarrow fresh plant juice concentrate in the range of 0.0001 to 10% by weight, based on the total weight of the cosmetic composition.